OBJECTIVES: Compliance with treatment is a key factor for successful treatment of chronic conditions like type 2 diabetes mellitus. Once-daily extended-release glipizide (GXL) has been showing more appealing in patient compliance. However, the data on comparison of GXL with other oral glucose-lowering drugs concerning compliance is limited. We tried to assess the compliance to GXL treatment for type 2 diabetes mellitus when compared with immediate-release glipizide(GIR). METHODS: We searched Medline, EMBASE, Cochrane Library, and the Chinese Biomedical database from their inception to end-Dec. 2009, as well as traced the reference lists. Randomized or non-randomized studies that reported medication compliance/adherence or persistence when using GXL versus GIR for treating the type 2 diabetes mellitus were included. Four reviewers judged trial eligibility and extracted data independently. We pooled trial data using the random-effect model and explored heterogeneity by using pre-specified variables. RESULTS: A total of 9 published studies (n=13 512) were included. GXL resulted in a 7% increase in compliance when compared with GIR (RD=0.07, 95%CI=0.06 to 0.08). The subgroup analyses showed that GXL increased patient compliance by 7% when compared with GIR in 4 retrospective database analyses (n=13 250, RD=0.07, 95%CI=0.05 to 0.10) and showed no difference in 5 randomized trials (n=262, RD=0.01, 95%CI=-0.03 to 0.05). There was no significant difference in patient compliance between fixed-dose GXL and GIR (RD=0.05, 95%CI=-0.01 to 0.11); however, the titrated-dose GXL significantly increased patient compliance by 6% (RD=0.06, 95%CI=0.03 to 0.09). When compared to GIR, GXL in long-term treatments (equal to or more than 1 year) increased patient compliance by 7% (RD=0.07, 95%CI=0.05 to 0.08), while no significant difference in short-term treatments (less than 1 year). CONCLUSIONS: When compared to immediate-release glipizide, extended-release glipizide could increase long-term patient compliance in retrospective database studies, while the increase in the short-term compliance to GXL was not observed.